The long-term objective of this work is to increase our fundamental understanding of ventricular fibrillation (VF) by mapping cardiac activation. Recent advances in (1) constructing mapping systems that can record from over 500 channels simultaneously, (2) building very small plunge electrodes for recording transmural potential, and (3) detecting local activation from the recorded potential during VF now make it possible to map cardiac activation sequences during VF. These techniques will be sued to answer three of the most important basic questions whose answers are necessary to understand VF. One, what are the electrophysiologic and anatomic variables responsible for the initiation of VF and how do they differ from those for ventricular tachycardia (VT)? Two, what are the electrophysiologic mechanisms responsible for the perpetuation of VF? Three, what are the electrophysiologic mechanisms within the heart by which the autonomic nervous system facilitates or inhibits the occurrences of VF? Studies to answer these questions will be performed in animal models of conditions thought to be associated with sudden death clinically, such as myocardial infarction. One study will be performed in humans undergoing cardiac surgery for implantation of an automatic defibrillator. Several hypotheses will be tested, some of which are mutually exclusive. One, that VF is maintained by figure of 8 and leading circle reentry which exhibits a moderate degree of organization with activation sequences that usually change gradually from cycle to cycle. Two, that VF is maintained by small disorganized wandering wavelets whose pathways seldom repeat. Three, that activation fronts during VF sometimes arise from foci. Four, that only a few activation fronts (perhaps less that ten) are present at any one time during the first minute of VF. Five, that a majority of the activation fronts in the left ventricle during VF arise from the subendocardium. Six, that VF and VT are maintained by the same mechanism (figure of 8 reentry), but that only a single reentrant circuit persists during VT because the activation occurs in a thin rim of tissue adjacent to an infarct, leading to a more stable pathway and a slower revolution time. Seven, that the figure of 8 reentry pattern during he initiation of VT can be created at numerous sites within the region of spared epicardium over a non-transmural infarct. Eight, that VT can be initiated from a thin layer of normal myocardium that does not contain patchy infarction or large inhomogeneities of refractoriness. Nine, that increased sympathetic tone in a peri-infarct zone will speed the rotational velocity of a reentrant pathway causing VT to become VF. Ten, that altered sympathetic tone in normal muscle outside an infarct zone will increase the case of induction of VF by causing secondary rotors to form in this non-infarcted tissue. The basic understanding of the fundamental mechanisms of VF gained from this work and of how these mechanisms are influenced by the presence of infarction and increased sympathetic tone should aid in the development of rational therapy to prevent and halt the number one health problem in the United States today, sudden cardiac death.